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BACKGROUND: Hirschsprung disease is commonly encountered by pediatric surgeons. Despite advances in the surgical management, these children may experience symptoms of bowel dysfunction throughout adulthood. Anorectal manometry may be used to assess post-operative anorectal structure and function. This review aimed to consolidate and evaluate the literature pertaining to post-operative findings of anorectal manometry in children with Hirschsprung disease. PURPOSE: (1) Synthesize the available data regarding anorectal motility patterns in children following repair of Hirschsprung disease. (2) Evaluate the reported anorectal manometry protocols. DATA SOURCES: We performed a systematic review of four databases: Embase, MEDLINE, the Cochrane Library, and PubMed. STUDY SELECTION: This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies reporting results of post-operative anorectal manometry in children with Hirschsprung disease were evaluated for inclusion. RESULTS: Twenty-three studies satisfied inclusion criteria, with a combined cohort of 939 patients. Post-operative anorectal manometry results were reported for 682 children. The majority of included studies were assessed as "poor quality." Disparate manometry protocols, heterogeneous cohorts, and lack of standardized outcome assessments introduced a risk of outcome reporting bias, limited the comparability of results, and impeded clinical translation of findings. CONCLUSIONS: This systematic review demonstrated the lack of high-quality evidence underlying the current understanding of post-operative anorectal motility in children with HD. There was little consistency in reported manometry outcomes between studies. In future work, emphasis must be placed on the application of standardized manometry protocols, cohort reporting, and patient outcome assessments.

BACKGROUND: Children with anorectal malformations may experience constipation and fecal incontinence following repair. The contribution of altered anorectal function to these persistent symptoms is relatively intuitive; however, colonic motility in this cohort is less well understood. Manometry may be used to directly assess colonic motility. PURPOSE: The purpose of this systematic review was to synthesize the available evidence regarding post-operative colonic motility in children with anorectal malformations and evaluate the reported equipment and protocols used to perform colonic manometry in this cohort. This systematic review was conducted in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We conducted a systematic review of four databases: Embase, MEDLINE, PubMed, and the Cochrane Library (1st January 1985-22nd July 2021). Studies reporting colonic manometry performed in children following anorectal malformation repair were assessed for eligibility. Data were extracted independently by two authors. Four studies were eligible for inclusion. Of the combined total cohort of 151 children, post-operative colonic manometry was conducted in 35. Insufficient reporting of medical characteristics, bowel function, and manometric outcomes restricted comparison between studies, and limited clinical applicability. No results from high-resolution colonic manometry were identified. Despite the prevalence of post-operative bowel dysfunction in children with repaired anorectal malformations, this systematic review highlighted the markedly limited evidence regarding post-operative colonic motility. This cohort may benefit from assessment with high-resolution techniques; however, future work must emphasize adherence to standardized manometry protocols, and include robust reporting of surgical characteristics, bowel function, and manometric outcomes.

BACKGROUND: A significant proportion of children experience bowel dysfunction (including constipation and fecal incontinence) following surgical repair of Hirschsprung disease (HD). Persistent symptoms are thought to relate to underlying colonic and/or anorectal dysmotility. Manometry may be used to investigate the gastrointestinal motility patterns of this population. PURPOSE: To (1) evaluate the colonic manometry equipment and protocols used in the assessment of the post-operative HD population and (2) summarize the available evidence regarding colonic motility patterns in children with HD following surgical repair. DATA SOURCES: We performed a systematic review of the Cochrane Library, Embase, MEDLINE, and PubMed databases (January 1, 1980 and March 9, 2020). Data were extracted independently by two authors. STUDY SELECTION: This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies reporting the post-operative assessment of children with HD using colonic manometry were considered for inclusion. RESULTS: Five studies satisfied selection criteria, providing a combined total of 496 children. Of these, 184 children with repaired HD underwent colonic manometry. Studies assessed heterogeneous populations, utilized variable manometry equipment and protocols, and reported limited baseline symptom characteristics, thus restricting comparability. All studies used low-resolution colonic manometry. CONCLUSIONS: This systematic review highlighted the paucity of evidence informing the understanding of colonic dysmotility in the post-operative HD cohort. Current literature is limited by variable methodologies, heterogeneous cohorts, and the lack of high-resolution manometry.

INTRODUCTION: Duodenal atresia (DA) is a congenital bowel obstruction requiring major surgery in the first week of life. Three morphological phenotypes are described, reflecting increasing degrees of obstruction and discontinuity of the duodenum. The cause of DA is not known. Tandler's original "solid cord" hypothesis conflicts with recent biological evidence, and is unable to account for differing DA types. In humans, a genetic etiology is supported by the association between Trisomy 21 and DA, and reports of familial inheritance patterns. Interruption of FGF10/FGFR2b signaling is the best demonstrated genetic link to DA in mice, with 35-75% of homozygous knockout embryos developing DA. PURPOSE: This review examines the current evidence surrounding the etiology of DA. We focus on research regarding FGF10/FGFR2b signaling and its role in duodenal and other intestinal atresia. Further, we outline planned future research in this area, that we consider necessary to validate and better understand this murine model in order to successfully translate this research into clinical practice. CONCLUSION: Determining the etiology of DA in humans is a clinical and scientific imperative. Fgf10/Fgfr2b murine models represent current science's best key to unlocking this mystery. However, further research is required to understand the complex role of FGF10/FGFR2b signaling in DA development. Such complexity is expected, given the lethality of their associated defects makes ubiquitous interruption of either Fgf10 or Fgfr2b genes an unlikely cause of DA in humans. Rather, local or tissue-specific mutation in Fgf10, Fgfr2b, or their downstream targets, is the hypothesized basis of DA etiology.

This article presents raw data obtained from a prospectively collected database of children with duodenal atresia at tertiary pediatric surgery hospital. For all potential participants, pertinent demographic, clinical and operative data was obtained from the database. Potential participants were then contacted and invited to complete a Pediatric Quality of Life Inventory (PedsQL™) 4.0 core score and gastrointestinal module questionnaires. Participant's response to each item in the questionnaires is provided, as well as their calculated health related quality of life scores. Data has the potential to be reused in future studies examining quality of life in duodenal atresia, paediatric gastrointestinal conditions, surgical neonatal conditions and children with trisomy 21. Further analysis and discussion is contained in related research article titled "Quality of life outcomes in children born with duodenal atresia" [1].

BACKGROUND: Anorectal malformations (ARM) are common congenital abnormalities of the terminal hindgut. Ideally, ARM should be diagnosed at, or shortly following, birth by careful physical examination of the perineum. Delayed diagnosis has been implicated as a risk factor for complications, including intestinal perforation. This study aimed to determine the rate of delayed diagnosis and associated intestinal perforation in ARM. METHODS: A retrospective review was performed for all ARM patients managed at The Royal Children's Hospital over a 16-year period (2000-2015). Data collected included ARM type, timing of diagnosis and complications. Delayed diagnosis was defined as being at more than 24 h of age. RESULTS: A total of 243 ARM patients (male 146/243, 60%) were included. The most frequent ARM types were perineal fistula (83/243, 34%) and rectovestibular fistula (40/243, 16%). Diagnosis was delayed beyond 24 h of age in 92 of 243 (38%) patients. The ARM type most commonly delayed in diagnosis was perineal fistula (37/83, 45%). Two patients in whom diagnosis was delayed suffered an intestinal perforation. CONCLUSION: Delayed diagnosis in ARM patients remains a common, and potentially fatal, occurrence. Improved assessment of newborns is required to ensure timely diagnosis of ARM, and avoidance of complications associated with delayed diagnosis.

BACKGROUND: Anorectal malformations (ARM) are common congenital abnormalities of the terminal hindgut. The high incidence of associated anomalies necessitates systematic screening, which should include renal and spinal ultrasonography, spinal radiography and an echocardiogram. This study aimed to determine the incidence of associated anomalies in ARM, and whether screening protocols were appropriately applied. METHODS: A retrospective review was performed of all ARM patients managed at The Royal Children's Hospital, Melbourne over a 16-year period (2000-2015). Data collected included ARM type, presence of associated anomalies, as well as utilization of renal and spinal ultrasonography, spinal radiography and echocardiography. RESULTS: A total of 243 patients (male 146/243, 60%) were reviewed. The most frequent ARM types were perineal fistula (83/243, 34%) and rectovestibular fistula (40/243, 16%). Full screening was performed in 153/243 (63%), while 18/243 (7%) received no screening. In fully screened patients, associated anomalies were diagnosed in 143/153 (93%), with cardiovascular, renal and musculoskeletal anomalies being most frequent. CONCLUSIONS: The high incidence of associated anomalies identified in fully screened ARM patients highlights the importance of systematic screening. Clinically significant anomalies may have been overlooked in the more than one-third of ARM patients in whom screening was absent or incomplete. Standardized screening protocols for ARM patients have now been implemented.

AIMS: Exclusion of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) from the diet is effective in alleviating symptoms of irritable bowel syndrome (IBS) in adults. Rapid-transit constipation (RTC) is a recently discovered subset of chronic constipation and has been linked to food intolerance. The aim of this study was to audit the effect of specific FODMAP elimination diets in children with RTC. METHODS: This was an audit of children presenting to a tertiary children's hospital surgeon with refractory chronic constipation who had rapid transit in the proximal colon on nuclear imaging; had hydrogen/methane breath tests for fructose, lactose, and/or sorbitol intolerance; and were advised to exclude positive sugar under clinical supervision. Patients filled in a questionnaire rating severity of constipation, abdominal pain, and pain on defecation with a visual analogue scale (VAS, 0 = none, 10 = high) and stool consistency for 6 months before and after dietary exclusion. RESULTS: In responses from 29 children (5-15 years, 21 males), 70% eliminated fructose, and 40% eliminated lactose. There was a significant reduction in the severity of constipation (VAS mean ± SEM, pre 5.8 ± 0.5 vs post 3.3 ± 0.6, P < 0.0001), abdominal pain (5.1 ± 0.6 vs 2.8 ± 0.5, P = 0.0004), pain on defecation (5.8 ± 0.6 vs 2.6 ± 0.5, P < 0.0001), and increase in stool wetness (Bristol Stool Scale pre 3.3 ± 0.3 vs post 3.9 ± 0.2, P = 0.004). CONCLUSION: Children with RTC showed significant improvements in constipation and pain after excluding the sugar indicated by positive breath tests, suggesting that specific sugar-exclusion diets may have a role in the management of RTC in children.

Background: Duodenal atresia (DA) is a congenital obstruction of the duodenum, which affects 1 in 7000 pregnancies and requires major surgery in the 1st days of life. Three morphological DA types are described. In humans, the association between DA and Down syndrome suggests an underlying, albeit elusive, genetic etiology. In mice, interruption of fibroblast growth factor 10 (Fgf10) gene signaling results in DA in 30-50% of embryos, supporting a genetic etiology. This study aims to validate the spectrum of DA in two novel strains of Fgf10 knock-out mice, in preparation for future and translational research. Methods: Two novel CRISPR Fgf10 knock-out mouse strains were derived and embryos generated by heterozygous plug-mating. E15.5-E19.5 embryos were genotyped with respect to Fgf10 and micro-dissected to determine the presence and type of DA. Results: One twenty seven embryos (32 wild-type, 34 heterozygous, 61 null) were analyzed. No wild-type or heterozygous embryos had DA. However, 74% of Fgf10 null embryos had DA (49% type 1, 18% type 2, and 33% type 3). Conclusion: Our CRISPR-derived strains showed higher penetrance of DA due to single-gene deletion of Fgf10 in mice than previously reported. Further, the DA type distribution in these mice more closely reiterated that observed in humans. Future experiments will document RNA and protein expression of FGF10 and its key downstream signaling targets in normal and atretic duodenum. This includes exploitation of modern, high-fidelity developmental tools, e.g., Fgf10 flox/+-tomatoflox/flox mice.

BACKGROUND AND AIM: Polyethylene glycol (PEG) is the gold standard for fecal disimpaction in constipation. A regimen of PEG combined with the stimulant laxative sodium picosulphate (SPS) produced fecal disimpaction in chronically constipated children in the community, but it is unknown if it is effective for more severe constipation. To determine the stool output and effect of a combined PEG and SPS regimen on fecaloma in children with severe constipation and impaction. METHODS: Children with symptoms for a duration of ≥2 years, a palpable fecaloma, and enlarged rectum on X-ray (rectal: pelvic ratio > 0.6) were recruited from a tertiary hospital. Daily diaries recorded laxative dose, stool frequency, volume, and consistency (Bristol stool scale, BSS). Abdominal X-rays were taken on day 1 and day 8, and stool loading was assessed using the Leech score. Laxative doses were based on the child's age. The dose of PEG with electrolytes taken was 2-8 sachets (14.7 g/sachet) on days 1-2, reducing to 2-6 sachets on day 3. The SPS dose was 15-20 drops on days 2-3. RESULTS: Eighty-nine children (4-18 years) produced a large volume of soft stool (median/inter-quartile-range: 2.2/1.6-3.1 L) over 7 days. Stool volume on X-rays decreased significantly in the colon (P < 0.001). Fecalomas resolved in 40 of 89 children, while 49 needed a second high dose. Rectal:pelvic ratios did not change. CONCLUSIONS: A combined high dose of PEG and SPS on days 1 and 2 was effective in removing the fecaloma in half of the children. Administering high doses for a longer period should be tested to provide outpatient disimpaction for severe fecalomas. Rectums remained flaccid after emptying.

BACKGROUND: Transcutaneous electrical stimulation (TES) using interferential current (IFC) is a new therapeutic treatment for constipation. Clinical studies show that TES-IFC for 3-6 months improves colonic transit, but it is not clear if short-term stimulation affects transit or the effect requires longer to develop. The aim of this study was to determine if TES-IFC for only four days affects oral-rectal transit time in healthy pigs. METHODS: Twenty-two 4-5-week old large white female piglets had transit studies during week 4 and week 5 by placing a capsule containing 18 radiopaque plastic markers in the esophagus under anesthetic followed by x-rays at 6, 30, 54, and 78 hours. Animals were randomly assigned to active or control groups. The active group received TES for 30 min daily for four days. Interferential current was applied through four electrodes (4 × 4 cm), with two para-spinal just below the last rib and two on the belly at the same level. Stimulation was at 4000 Hz and 4080-4160 Hz with currents crossing through the abdominal cavity. RESULTS: Whole bowel transit times ranged from 7.7 to 72.2 hours, stomach transit from <1 to 63 hours, and bowel with rectum transit time from 5 to 53 hours. Transit times were the same for the control (median 28.4 hours) and TES-IFC (23.0 hours) groups in the prestimulation and stimulation weeks (control 23.0, TES-IFC 19.8 hours) with no change within or between groups. CONCLUSION: Four days of half-hour TES-IFC daily in healthy 5-week-old piglets did not change oral-rectal transit time.

Multiple endocrine neoplasia 2B (MEN2B) is a rare syndrome caused by an activating mutation of the RET gene, leading to enteric gangliomatosis. This child presented with constipation at 1-mo old, was diagnosed with MEN2B by rectal biopsy at 4 mo, had thyroidectomy at 9 mo and a colectomy at 4 years. We studied the extent of neuronal and nerve fibre proliferation and which classes of enteric nerves are affected by examining the colon with multiple neuronal antibodies. Resected transverse colon was fixed, frozen, sectioned and processed for fluorescence immunohistochemistry labelling with antibodies against TUJ1, Hu, ChAT, NOS, VIP, SP and CGRP and cKit. Control transverse colon was from the normal margin of Hirschsprung (HSCR) colon (4-year-old) and a child with familial adenomatous polyposis (FAP, 12 year). Myenteric ganglia were increased in size to as wide as the circular muscle. There was a large increase in nerve cells and nerve fibres. ChAT-, NOS-, VIP- and SP-immunoreactive nerve fibres all increased in the myenteric ganglia. NOS-IR nerves preferentially increased in the muscle, while VIP and SP increased in submucosal ganglia and mucosal nerve fibres. The density of ICC was normal. RET overactivation in MEN2B lead to a large increase in intrinsic nerve fibres in the myenteric and submucosal ganglia, with a relative increase in NOS-IR nerve fibres in the circular muscle and VIP and SP in the submucosal ganglia and mucosa. The changes were associated with severe constipation resulting in colectomy at 4 years.

Undescended testis (UDT) occurs when something goes wrong with testicular descent from high in the abdominal cavity to the scrotum. Normal descent occurs in two steps, with the transabdominal phase controlled by a new testicular hormone, insulin-like hormone 3, and the inguinoscrotal phase controlled by androgens. The latter phase requires a complex process of migration from the inguinal abdominal wall to the scrotum and is commonly defective, leading to the high incidence (2-4%) of UDT at birth. The clinical examination of babies and infants aims to confirm the persistence of congenital UDT by 3-6 months, so surgery can be optimally timed at 6-12 months. For those boys who develop acquired UDT later in childhood, the 'ascending' testis often needs surgery between 5 years and 10 years, so all boys should be screened again for UDT at school entry.

BACKGROUND & AIMS: Hirschsprung disease (HSCR) is caused by failure of cells derived from the neural crest (NC) to colonize the distal bowel in early embryogenesis, resulting in absence of the enteric nervous system (ENS) and failure of intestinal transit postnatally. Treatment is by distal bowel resection, but neural cell replacement may be an alternative. We tested whether aneuronal (aganglionic) colon tissue from patients may be colonized by autologous ENS-derived cells. METHODS: Cells were obtained and cryopreserved from 31 HSCR patients from the proximal resection margin of colon, and ENS cells were isolated using flow cytometry for the NC marker p75 (nine patients). Aneuronal colon tissue was obtained from the distal resection margin (23 patients). ENS cells were assessed for NC markers immunohistologically and by quantitative reverse-transcription polymerase chain reaction, and mitosis was detected by ethynyl-2'-deoxyuridine labeling. The ability of human HSCR postnatal ENS-derived cells to colonize the embryonic intestine was demonstrated by organ coculture with avian embryo gut, and the ability of human postnatal HSCR aneuronal colon muscle to support ENS formation was tested by organ coculture with embryonic mouse ENS cells. Finally, the ability of HSCR patient ENS cells to colonize autologous aneuronal colon muscle tissue was assessed. RESULTS: ENS-derived p75-sorted cells from patients expressed multiple NC progenitor and differentiation markers and proliferated in culture under conditions simulating Wnt signaling. In organ culture, patient ENS cells migrated appropriately in aneural quail embryo gut, and mouse embryo ENS cells rapidly spread, differentiated, and extended axons in patient aneuronal colon muscle tissue. Postnatal ENS cells derived from HSCR patients colonized autologous aneuronal colon tissue in cocultures, proliferating and differentiating as neurons and glia. CONCLUSIONS: NC-lineage cells can be obtained from HSCR patient colon and can

BACKGROUND: When primary care of constipation fails, the patient may need emergency hospitalisation for disimpaction. This study aimed to provide population-based data on the number of unplanned admissions and the cost to the healthcare system for constipation in Victoria, Australia in financial year 2010-11. METHODS: The Victorian Admitted Episodes Dataset was examined to find the number of emergency hospital separations coded as constipation (ICD-10-AM Code K390). An estimate of costs was determined from the number of weighted inlier equivalent separations (WIES) multiplied by the WEIS price, used by the Victorian Government for funding purposes. RESULTS: There were 3978 emergency separations for constipation in Victoria in 2010-2011, 92% in public hospitals. Fifty-five percent were female and 38% > 75 years old. One third stayed overnight and 1/3 more than 1 day. The emergency bed day rate was 7.1 per 10,000 of population. The estimate of cost, based on WEIS, was approximately $8.3 million. Potential savings could be made by reducing the number of separations in 6 Local Government Areas (LGAs). CONCLUSIONS: This study shows that the burden (in number of admissions, emergency bed days and overall direct costs) in managing emergency admissions for constipation in Victoria, Australia, is very significant and likely to be similar in other developed countries. Improved primary healthcare and alternative ways to achieve faecal disimpaction without emergency admission could save the public health system a proportion of this $8.3 million.

OBJECTIVE: In developing countries like Bangladesh, delayed presentation for disorders of sex development (DSD) is common, and provides some special problems for management. There remains significant controversy about appropriate sex assignment in this group. We aimed, therefore, to assess gender identity (GI) in 50 consecutive patients with DSD presenting to a referral centre in Chittagong, Bangladesh, and correlate it with Prader score, to see if the latter could be used to predict GI. METHODS: A cross-sectional, case-control study of 50 consecutive children with DSD and 50 children with vascular anomalies was conducted in the Pediatric Surgical Clinic, Chittagong Medical College and Hospital. After informed consent, patients and controls provided oral answers to a GI questionnaire and had a detailed history and physical examination. Sex-typed activities were assessed by observations of a structured toy play and the child's selection of a toy to keep. Both patients and parents then completed the Child Game Participation Questionnaire. RESULTS: There were no differences in age (2-16 years, mean 8.74) between controls and DSD patients (11 46, XX DSD, 32 46, XY DSD, 4 MGD, 3 ovo-testicular DSD). Fifteen of the DSD patients (30 %) came from consanguineous marriages and only 2 of the control patients had consanguinity of their parents. For the 13-question GI interview, there was no overall difference between DSD cases and controls. For the 46, XX DSD subgroup, there was a significantly higher score (11.1 ± 7.1) compared with control girls (4.5 ± 4.7) (p < 0.05), while for DSD and control boys, there was a positive correlation with age and GI (p < 0.01). Prader score correlated with GI score in both control (r = 0.91) and DSD patients (r = 0.75) (p < 0.01), DSD girls played significantly less with girls' toys than controls (p < 0.01), but there was no differences for the boys. Composite scores on GI and gender-related behaviour correlated with Prader score for DSD patie

To permit normal postnatal germ cell development, the mammalian testis undergoes a complex, multi-staged process of descent to the scrotum. Failure of any part of this process leads to congenital cryptorchidism, wherein the malpositioned testis finds itself at the wrong temperature after birth, which leads to secondary germ cell loss and later infertility and risk of cancer. Recent studies suggest that neonatal gonocytes transform into the putative spermatogenic stem cells between 3 and 9 months, and this initial postnatal step is deranged in cryptorchid testes. In addition, it is thought the abnormality high temperature may also impair apoptosis of remaining gonocytes, allowing some to persist to become the possible source of carcinoma in situ and malignancy after puberty. The biology of postnatal germ cell development is of intense interest, as it is likely to be the key to the optimal timing for orchidopexy.

We present the case of a boy with antenatally diagnosed bilateral testicular microlithiasis. Following annual surveillance the child developed metachronous bilateral epidermoid cysts. These were subsequently excised with testicular sparing surgery. Currently, there are only three cases of bilateral epidermoid cysts in the paediatric population, and none have been associated with testicular microlithiasis. This reignites the discussion regarding the histogenesis of epidermoid cysts and how its pathophysiology might relate to testicular microlithiasis.